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OBJECTIVE: There is limited pharmacokinetic data available for the combination artesunate + amodiaquine, which is used widely to treat uncomplicated malaria. This study examines the bioavailability and tolerability of a fixed (200 mg artesunate + 540 mg amodiaquine) and loose (200 mg + 612 mg) combination with a 2x2 cross-over design in 24 healthy volunteers. METHODS: Parent compounds and metabolites [dihydroartemisinin (DHA) and desethylamodiaquine (DEAQ)] were measured by high-performance liquid chromatography-electrochemical detection, and the area under the curve (AUC)(0-t) and C(max) were compared by an analysis of variance (ANOVA) based on geometric least square means using the Schuirmann two one-sided test. RESULTS: The AUC(0-t) for total DHA and DEAQ were 1522 +/- 633 and 30021 +/- 14211 ng h/ml for the fixed products and 1688 +/- 767 and 40261 +/- 19824 ng h/ml (mean +/- standard deviation) for the loose products. The ANOVA showed no statistical differences except for sequence effect for DHA. The values obtained with the fixed product were within the 125% bioequivalent limits but extend below the 80% bioequivalence limits. CONCLUSION: Both combinations were well tolerated and had comparable pharmacokinetic profiles; differences are unlikely to be clinically relevant.

Original publication

DOI

10.1007/s00228-009-0656-1

Type

Journal

European journal of clinical pharmacology

Publication Date

08/2009

Volume

65

Pages

809 - 821

Addresses

National Center for Drug Research (CRD), Universiti Sains Malaysia (USM), 11800 Minden, Pulau Pinang, Penang, Malaysia.

Keywords

Humans, Artemisinins, Amodiaquine, Biological Markers, Drug Combinations, Antimalarials, Drug Therapy, Combination, Analysis of Variance, Area Under Curve, Chi-Square Distribution, Cross-Over Studies, Biological Availability, Time Factors, Reference Values, Adult, Asian Continental Ancestry Group, Malaysia, Female, Male